1. Field of the Invention
The present invention relates to a multiple single nucleotide polymorphism (SNP) for diagnosing colorectal cancer, a microarray and a kit including the same, and a method of diagnosing colorectal cancer using the same.
2. Description of the Related Art
The genomes of all organisms undergo spontaneous mutation in the course of their continuing evolution, generating variant forms of progenitor nucleic acid sequences (Gusella, Ann. Rev. Biochem. 55, 831-854, 1986). The variant forms of progenitor nucleic acid sequences may confer an evolutionary advantage or disadvantage, or may be neutral relative to a progenitor form. In some instances, a variant form confers a lethal disadvantage and is not transmitted to subsequent generations of the organism. In other instances, a variant form confers an evolutionary advantage to the species and is eventually incorporated into the DNA of most members of the species and effectively becomes the progenitor form. In many instances, both progenitor and a variant forms survive and coexist in a species population. The coexistence of multiple forms of a sequence gives rise to polymorphisms.
Several types of polymorphisms are known, including restriction fragment length polymorphism (RFLP), short tandem repeats (STR) and single nucleotide polymorphism (SNP). Among them, SNPs take the form of single nucleotide variations among individuals of the same species. When SNPs occur in protein coding sequences, some of the polymorphic forms may give rise to the non-synonymous change of amino acid causing expression of a defective or a variant protein. On the other hand, when a SNP occurs in non-coding sequences, some of these polymorphisms may cause the expression of defective or variant proteins as a result of defective splicing, for example. Other SNPs have no phenotypic effect.
It is estimated that human SNPs occur at a frequency of 1 in every 1,000 bp. When such SNPs induce a phenotypic expression such as a disease, polynucleotides containing the SNPs can be used as a primer or a probe for diagnosis of the disease. Monoclonal antibodies specifically binding with the SNPs can also be used in the diagnosis of the disease. Currently, research into the nucleotide sequences and functions of SNPs is being performed by many research institutes. The nucleotide sequences and the results of other experiments on the identified human SNPs have been put in databases to be easily accessible.
Even though findings available to date show that specific SNPs exist in human genomes or cDNAs, the phenotypic effects of SNP's have not been revealed. Functions of most SNPs have not yet been discovered.
Most colorectal cancers are pathologically adenocarcinoma and roughly divided into colon cancer and rectal cancer according to the region in which the cancer occurs. The incidence of rectal cancer is highest at about 50%. According to recent research, the incidence of colorectal cancer and the death rate due to colorectal cancer are significantly increasing in Korea due to eating habit changes. The incidence of colorectal cancer increased by 420% from 1995 to 2002 and was the most common type of cancer (2003's Health insurance statistics, Korean National Health Insurance Corporation).
Causes of colorectal cancer are not clearly revealed, but genetic factors, eating habits related to high fat and low fiber diets, and inflammatory bowel disease are contributory factors. Colorectal cancer can occur in all age groups. As age increases, the incidence of colorectal cancer increases, and the 50-70 age bracket has a high incidence. Colon cancer often occurs in females and rectal cancer often occurs in males.
Treatment of colorectal cancer is based on surgical excision, which is performed in parallel with cancer chemotherapy and radiation therapy. In spite of the advancement of surgical therapy, cancer chemotherapy and radiation therapy, a dramatic improvement in prognosis is not achieved once the cancer has occurred. The average five-year survival rate is 90% or more for stage I, 70% or more for stage II, 50% or more for stage III, and 5% or less for stage IV (Information for Cancer, 2004, National Cancer Center).
As described above, when colorectal cancer is early detected and treated, accordingly the survival rate is significantly increased. Thus, early diagnosis of colorectal cancer is urgently required. The diagnosis of colorectal cancer is performed by rectal digital examination, stool occult blood examination, and barium enema for patients that have colorectal disease-related symptoms. If necessary, histologic examination through sigmoidoscopy and colonoscopy is performed.
However, conventional methods as described above have low diagnostic accuracy, cannot early diagnose colorectal cancer before it occurs, and are uncomfortable for the subject being examined.
Intensive investigations made by the present inventors in view of the above existing circumstances have resulted in finding that all individuals having colorectal cancer have the same specific SNPs, and the SNPs make it possible to predict the incidence probability of and genetic susceptibility to colorectal cancer, and have come to complete the present invention.